New substituted 2-(phenylaminomethyl)-benzimidazoles, used as thrombin inhibitors, serine protease inhibitors, antithrombotic agents and intermediates

摘要

1-Alkyl-2-(4-substituted phenylaminomethyl)-benzimidazole derivatives (I) are new. 1-Alkyl-2-(4-substituted phenylaminomethyl)-benzimidazole derivatives of formula (I) and their tautomers, stereoisomers, mixtures, prodrugs, derivatives (having carboxy groups replaced by groups which are negatively charged under physiological conditions) and salts are new. Ra = 1-3C n-alkyl (optionally substituted by one or more F), which is substituted in the 1-position by (a) (i) pyrrolidinocarbonyl or 2,5-dihydropyrrolocarbonyl (both optionally substituted by 1-3C alkyl) plus (ii) NHQ1 or (b) 1-3C alkyl terminally substituted by Q2; Q1 = carboxy-(1-4C) alkyl, cyano-(1-4C) alkyl or tetrazolyl-(1-4C) alkyl; Q2 = N-(carboxy-(1-3C) alkylaminocarbonyl)-amino (optionally substituted by 1-3C alkyl on either or both amino group(s)), carboxy-(1-3C) alkoxy, N-(carboxy-(1-3C) alkyl)-amino, N-(1-3C alkyl)-N-(carboxy-(1-3C) alkyl)-amino, N-(carboxy-(1-3C) alkylsulfonyl)-amino, N-(1-3C alkyl)-N-(carboxy-(1-3C) alkylsulfonyl)-amino or tetrazolyl-(1-3C) alkyl; Rb = 1-3C alkyl; Rc = amidino, CN or 5-(Q3)-1,2,4-oxadiazol-3-yl, and Q3 = 1-3C alkyl or phenyl (optionally substituted by F, Cl, Br or 1-3C alkyl). An Independent claim is included for the preparation of (I).